Strictly speaking, fulminant hepatic failure associated with Wilson disease (WD-FHF) is not “acute liver failure,” because there is an underlying (although unrecognized) chronic liver disease. When WD-FHF was first reported in the late 1970s, it seemed that it might be extremely rare. In fact, it accounts for approximately 5% of patients with acute liver failure. Besides severe coagulopathy and encephalopathy, WD-FHF patients have a typical clinical profile: Coombs-negative hemolytic anemia with features of acute intravascular hemolysis, only modest increases in serum aminotransferases, normal or markedly subnormal serum alkaline phosphatase, and rapid progression to renal failure. Females are more likely than males to develop WD-FHF. Thus, the presented case appears classic. The intravascular hemolysis reflects copper toxicity to erythrocyte plasma membranes. The serum aminotransferase activities may be lower than expected because the liver is undergoing extensive hepatocellular apoptosis or because it is already cirrhotic. Serum alkaline phosphatase is typically subnormal, although not always as low as in this case; the mechanism for this feature remains obscure. Serum and urinary copper concentrations are greatly increased in WD-FHF, but these laboratory results may not be available in time for critical clinical decision-making. Whereas serum ceruloplasmin is not informative for making the diagnosis of WD-FHF, formulas that use available laboratory data [a ratio of alkaline phosphatase (in U/L) to total bilirubin (in milligrams per deciliter) <4, concomitantly with an aspartate aminotransferase–alanine aminotransferase ratio >2.2] are useful.
The standard teaching is that WD-FHF is uniformly fatal, and thus liver transplantation is required. This concept should be the mindset. It mandates rapid diagnosis, immediate/timely transfer to a liver transplantation center, and extensive communication with the patient and his/her family. The use of standard chelators alone has little efficacy in treating WD-FHF; the role of antioxidants as adjunctive therapy is being investigated. Recent experience has shown that plasmapheresis and hemofiltration, exchange transfusion, or albumin dialysis may stabilize patients with WD-FHF until transplantation. Very occasionally (as in this case), such interventions may obviate transplantation. Arrangements for liver transplantation should be completed anyway. If a brother or sister is a potential donor, he/she needs to be assessed for WD, preferably by genetic diagnosis. WD carriers (heterozygotes, e.g., parents) can be donors.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: None declared.
Consultant or Advisory Role: E.A. Roberts, Bristol-Myers Squibb.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: None declared.
Expert Testimony: None declared.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication November 15, 2010.
- Accepted for publication December 3, 2010.
- © 2010 The American Association for Clinical Chemistry